Superparamagnetic nanosensors for the detection of cardiovascular biomarkers by magnetic resonance relaxometry and imaging

Superparamagnetic nanosensors for the detection of cardiovascular biomarkers by
magnetic resonance relaxometry and imaging
Advanced Imaging Unit. Dpt of Epidemiology, Atherothrombosis and Imaging. Spanish Cardiovascular Research Centre (CNIC) and Spanish Pulmonary Research Centre (CIBERES). C/ Melchor Fernández-Almagro 3, 28029 Madrid.bsalinas@cnic.es
Purpose: Magnetic Resonance Relaxometry (MRR) and Magnetic resonance imaging (MRI) are increasingly accessible techniques for in vitro and in vivo diagnosis and quantification. With this in mind our aim was to develop two different superparamagnetic nanosensors for the detection and quantification of Ca2+ ions and Matrixmetalloproteases 2 and 9 (MMPs). Both nanosensors are based in the same principle, i.e. the change in the relaxometric properties of the particles due to the interaction with the sample.Materials and Methods: Iron oxide nanoparticles (SPIO) were synthesised by thermal decomposition of organic precursors. These SPIOs were reacted with 2-(acryloyloxy)ethyl succinate by olefin metathesis in presence of Grubbs-Hoveyda 2nd generation catalyst. Water stable NPs generated in just one step were redispersed in aqueous solution with different Ca2+ concentrations. The formation of clusters between the terminal carboxyl groups and the cations generate changes in the r2 relaxometric values which subsequently were observed and demostrated in MRI. The selectivity was checked by measuring with other important ions like Al3+,Mg2+,NH4+,K+,Cu2+ and Na+ by MRR and MRI. For the synthesis of the second nanosensor, for MMP detection and quantification, a different approach was used. SPIOs were oxidized with KMnO4, generating water stable nanoparticles with azelaic acid as surfactant. The terminal carboxylic groups present in the surface were activated with EDC and sulfo NHS and conjugated with gelatin. The relaxivity of these NPs was studied in presence of MMPs 2 and 9, along time, by MRM and MRI. Conclusions: We developed, by new functionalization tecniques, two new superparamagnetic nanosensors. The first one is selective of Ca2+ versus Al3+, Mg2+, NH +
4 , K+, Cu2+ and Na+. It allows for the quantification of calcium due to the changes in
its physicochemical properties, this has been confirmed by imaging and analytical techniques. The second nanosensor is able to selectively quantify the amount of MMP2 and -9 with a detection limit as low as 1 ng/mL, smal er than most commercial kits, without any special sample preparation. Also for this sensor various techniques have been used to demonstrate it mechanism of action. Finally we wil show the possibilities of both nanosensors for in vivo use.References:1.-B. Salinas, J. Ruiz-Cabello, I. Bilbao, M. P. Morales, E. G. Rodríguez, P. Martin3, F. Herranz. ACS Nano, submitted.2.-B. Salinas; J. Ruiz-Cabel o; M. P. Morales; F. Herranz. Bioinspired, Biomimetic and Nanobiomaterials. 2012, 1 - 3, 166 - 172.3.-F. Herranz; M.P. Morales; A. Roca; M. Desco; J. Ruiz-Cabel o. Chem. Eur. J. 2008, 14, 9126-9130.4.- F. Herranz; M. P. Morales; A. Roca; R. Vilar; J. Ruiz-Cabello. Contrast Media Mol. Imaging. 2008, 3, 215-222

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